In the practice of human and veterinary medicine, it is often desirable and necessary to use various polymeric devices such as urinary catheters, cerebro peritoneal shunts, breast implants, artificial joints, hemodialysis devices and the like to treat or diagnose disease. Such devices, although manufactured from inert polymers, most commonly silicones, are often conduits for infection from surface bacteria or become nonfunctional due to surface blood clotting if they are in prolonged contact with the vascular system. Further, some devices, such as irrigating or drainage tubes and catheters, are uniquely positioned to be therapeutic drug delivery systems. Other devices can be anatomically positioned to effect physiologic function, such as inhibitors or enhancers of fertility and for cancer chemotherapy. All such diagnostic, preventive and/or therapeutic functions of the polymeric devices are dependent upon the unique relation between the polymer and the medicinal agent which will be outlined in this invention.
These devices are often contaminated by bacteria, fungus, viruses and other organisms or infective proteins, resulting in systemic and/or local infection. Such contaminants sometimes lead to sepsis and death. This phenomenon is further aggravated by contact of the device, such as urinary tract Foley type catheters, for example, by external mammalian tissues, such as skin or mucous membranes which themselves are carriers of potentially infective organisms.
Various proposals have been made in the past to provide protection for such devices such as catheters and various bacteriostats and bacteriocides have been applied to the surfaces of urinary catheters to prevent infection. However, none of these have been completely effective and the danger of infection and the potentially fatal problems it presents is always present, particularly in the case of indwelling catheters such as urinary tract Foley type catheters.
It has also been believed that therapeutic risk involved with the use of medical devices could be controlled, eliminated or attenuated if the device itself had antiseptic properties. Medical use and research has demonstrated that antibiotic use alone such as systemic treatment separate from local application to the device, is ineffective for long term antisepsis due to bacterial resistance and sometimes drug allergic reaction. Therefore, the use of an antiseptic agent whose anti-infective organism-effects are multi focal and wide-spectra is necessary if long term and safe anti-sepsis is to be imported to the device. It has become readily apparent that many agents, while not developing microorganism resistance, have a limited spectrum such as nitrofurazone and chloroxylenol, which are weakly effective against Pseudomonas and some Proteus, silver sulfadiazine, which is weakly effective against Staphylococcus aureus and Pseudomonas, and mandelic acid, which is weakly effective against Proteus. It has accordingly not been possible to achieve reliable long term indwelling of catheters, such as urinary catheters, capable of effective antiseptic action.
This problem has been especially prevalent in urinary retention catheters such as Foley catheters. Retention catheters connect the patient's bladder to an outside collecting system to continuously remove urine from the patient's bladder. Sources of urinary retention catheter related urinary tract infections are suspected to be bacteria progressing from the patient's meatus through the peri-urethral space into the bladder or the catheter lumen. A number of methods and devices in the prior art for attempting to prevent bacterial caused urinary tract infections are disclosed. Examples include U.S. Pat. Nos. 4,773,901; 5,098,379; 5,236,422; 5,261,896; 5,269,755 and 5,269,770. However, for many applications, these devices have not proved to be totally effective. As a result, a substantial probability of acquiring a urinary tract infection still exists when using these devices.
In addition to the contamination and infection difficulties discussed above, it is further highly desirable in many procedures to alternatively provide medicaments for other purposes. For example, it is often necessary and desirable to have catheters, tubes and other medical devices in contact with the animal or human bloodstream to deliver medication, perform hemodialysis or other therapeutic and/or diagnostic functions. These indwelling devices and their lumens often become obstructed by clotted blood rendering them non-functional. It is, therefore, important that a reliable means be provided to ensure that an effective amount of anticoagulant is administered to the problem location to prevent undesirable blood coagulation/clotting.
There are also circumstances in which formation of scar tissue is highly undesirable. This can occur during the healing of naturally occurring wounds or as a result of surgical procedures. It is beneficial and needed in both animal and human medicine to modify or "remodel" the scar formed after injury or surgery in order to effect a more near normal function. This is evident in contracture caused by burn scar, urethral stenosis following prostate surgery or injury, tracheal stenosis, in flexor tendon repair in the hand and in other procedures. However, there is a need for a vehicle in which "scar remodeller" compounds that assist in such scar modification can be reliably and continuously applied to the target tissue. Prior attempts and devices have not been completely successful in that regard.
There are many other uses for medicated polymeric devices such as implanted spermicidal devices and chemotherapeutic delivery systems.